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A.L. Cannon, A.J. Barber, Penn State Retina Research Group; Expression of synapse–specific proteins in the rat retina is altered by experimental diabetes . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3236.
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Purpose: Previously we found that experimental diabetes in rats increased retinal cell apoptosis and after several months, the thickness of the inner plexiform layer and the number of retinal ganglion cells were significantly reduced (Barber et al, 1998, JCI, 102:783–791). These data suggested that diabetes induces a chronic neurodegeneration in the inner retina. The aim of this study was to determine how diabetes alters the expression of synapse–specific proteins in the retina. Methods: Male Sprague–Dawley rats were made diabetic by injection of streptozotocin (STZ) and sacrificed three months later. The content of the synaptic proteins synaptophysin, CaMKII, and phospho–CaMKII were quantified by immunoblotting whole retina lysates. Subunits of the N–methyl–D–aspartate (NMDA) receptor were quantified by immunoblotting synaptic plasma membrane fractions. The distribution of synaptophysin was also examined by immunohistochemistry. Results: STZ–diabetic rats had significantly higher blood glucose compared to controls (343.3±28.66 Vs 92.3±3.59 mg/dL, p<0.001) and weighed significantly less than controls (363.9±16.00 Vs 557.4±22.80 gm, p<0.001). Synaptophysin was significantly reduced by STZ–diabetes to approximately 75% of control values (p<0.05) but there was no change in total CaMKII, phospho–CaMKII or beta–actin in the same samples. Synaptophysin immunoreactivity was also diminished in cryostat sections of retinas from STZ–diabetic rats compared to controls. The content of the NMDA R2a subunit was also reduced in the synaptic plasma membrane fractions from STZ–diabetic rats, compared to controls (p<0.05). Conclusions: These data suggest that the content of a specific subset of synaptic proteins is reduced in the retinas of experimentally diabetic rats. Therefore, diabetes may influence individual features of synaptic function. Reduced vision in diabetic retinopathy may in part be due to the way these specific deficits compromise neurotransmisson in the retina.
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